The present invention relates to novel cross-linkers for hydrogels, in particular for hyaluronan hydrogels, corresponding hydrogels including said cross-linkers and various applications thereof.
The future challenges of an aging society and associated health problems such as the increasing need for regenerative medical devices have stimulated worldwide research efforts in the field of tissue engineering. Particular attention has been focused on hydrogels including those made from polymers such as polyethylene glycol diacrylates (PEG-DA), polyglycerol diacrylates and chemically modified hyaluronic acid (HA) such as thiolated HA (HA-SH), exploiting their hydrophilicity as well as high biocompatibility.
Hyaluronic acid is an evolutionary well-preserved linear, polycationic sugar found in all connective tissues that can promote elastin formation in tissue culture. HA-based hydrogels have been studied extensively and are used in a wide variety of applications such as for medical implants, tissue engineering, cell culture and drug delivery.
However, hyaluronic acid is not a bio-inactive material. For example, HA and its derivatives can be degraded by hyaluronidases to short fragments, causing undesirable side reactions. Moreover, many cells having specific membrane receptors, such as CD44, LYVE1 or RHAMM, can bind to HA and interact therewith.
In view of these shortcomings of HA hydrogels of the prior art, an object of the present invention is to provide improved HA hydrogels which maintain the advantages of the known HA gels but which are bio-inactive or whose bioactivity is adjustable on demand.
A further related object of the invention is to provide means for preparing such hydrogels.
These objects are achieved by providing the cross-linker and the hydrogel of the invention.